A role for dendritic cells in the dissemination of mycobacterial infection

Humphreys, Ian R.; Stewart, Graham R.; Turner, David J.; Patel, Janisha; Karamanou, Danai; Snelgrove, Robert J.; Young, Douglas B.

doi:10.1016/j.micinf.2005.12.023

Cited by 103 publications

(93 citation statements)

References 24 publications

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“…Although the role of pathogens in the migration of LDCs has previously been reported in several models of viral (43)(44)(45) or Mycobacterium tuberculosis (46,47) infection, we describe for the first time the very rapid kinetics of pathogen migration using LDCs.…”

Section: Discussionmentioning

confidence: 79%

Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route

Cleret

Quesnel‐Hellmann

Vallon-Eberhard

et al. 2007

The Journal of Immunology

138

121

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Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially because anthrax is an emerging bioterrorism agent. The exact mechanisms leading to a severe clinical form through the inhalational route are still unclear, particularly how immobile spores are captured in the alveoli and transported to the lymph nodes in the early steps of infection. We investigated the roles of alveolar macrophages and lung dendritic cells (LDC) in spore migration. We demonstrate that alveolar macrophages are the first cells to phagocytose alveolar spores, and do so within 10 min. However, interstitial LDCs capture spores present in the alveoli within 30 min without crossing the epithelial barrier suggesting a specific mechanism for rapid alveolus sampling by transepithelial extension. We show that interstitial LDCs constitute the cell population that transports spores into the thoracic lymph nodes from within 30 min to 72 h after intranasal infection. Our results demonstrate that LDCs are central to spore transport immediately after infection. The rapid kinetics of pathogen transport may contribute to the clinical features of inhalational anthrax.

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Section: Discussionmentioning

confidence: 79%

Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route

Cleret

Quesnel‐Hellmann

Vallon-Eberhard

et al. 2007

The Journal of Immunology

138

121

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“…Taking into account that the differentiation into DC from circulating Mos occurs in vivo [52,53] and that DCs derived from Mos constitute the major DC subset involved in mycobacterial infections [17,18,54], our findings may be relevant to understand the DC deficiencies observed in patients with active TB [23,55,56]. Furthermore, our results could be also relevant in other diseases characterized by high CD16 + Mo numbers, such as HIV, rheumatoid arthritis, sepsis, atherosclerosis, Kawasaki disease, and hemolytic uremic syndrome, among others [57].…”

Section: Discussionmentioning

confidence: 99%

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

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Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16 + /CD16 − Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16 − Mos differentiated into CD1a + DC-SIGN high cells achieving an efficient recall response, while CD16 + Mos differentiated into a CD1a − DC-SIGN low population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16 + Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16 − Mo differentiation. Furthermore, depletion of CD16 + Mos indeed improved the differentiation of Mos from TB patients toward CD1a + DC-SIGN high DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16 + Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs. Keywords: Dendritic cells r Monocyte differentiation r Tuberculosis See accompanying Commentary by Lugo-Villarino and NeyrollesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMonocytes (Mos) are large circulating leukocytes of the myeloid lineage that mediate essential functions of innate immunity including phagocytosis and cytokine production [1,2]. Mos are produced Correspondence: Dr. Luciana Balboa e-mail: luciana_balboa@hotmail.com in the bone marrow and released into the blood, and circulate in blood or reside in a spleen reservoir and, upon tissue infiltration they can differentiate into macrophages (M s) or DCs. Although human blood Mos are a highly heterogeneous population, two main subsets have been described: CD14 + CD16 − "classical" Mos are the major Mo population and CD14 + CD16 + Mos, the minor one (5-10% of total Mos). The latter subset has a more mature phenotype and an enhanced proinflammatory activity [3]. This heterogeneity has led to the hypothesis that Mos are committed to specific functions prior to tissue infiltration [4]. Also, C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 336Luciana Balboa et al. Eur. J. Immunol. 2013. 43: 335-347 an imbalance in the relative proportions of the subsets during acute inflammation [5] and several infectious diseases [6][7][8][9][10] including tuberculosis (TB) [11,12] has been described. TB, a disease that mainly affects the respiratory system, infects onethird of the world's population and kills 2 million people each year [13]. The success o...

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“…tuberculosis is a facultative intracellular pathogen. Evidence that M. tuberculosis resides in macrophages has been known at least since the studies of Sabin and colleagues in the 1920s (65,220), although the spectrum of cells in which the bacteria reside in vivo has been recently found to include myeloid dendritic cells (129,244,269). Macrophages and dendritic cells serve as cells that present antigen to T lymphocytes and secrete cytokines that direct the differentiation and modulation of T lymphocytes.…”

Section: Mechanisms Of Immunity To Mycobacterium Tuberculosismentioning

confidence: 99%

HIV and Tuberculosis: a Deadly Human Syndemic

2011

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SUMMARY A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.

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A role for dendritic cells in the dissemination of mycobacterial infection

Cited by 103 publications

References 24 publications

Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route

Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

HIV and Tuberculosis: a Deadly Human Syndemic

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